The invention relates to compositions comprising red rice fermentation product, that can be used to treat osteoporosis and related abnormal bone mass conditions in mammals, including humans.
Red Rice in Ancient China
Red rice is known mostly for its use in food as a preservative and colorant and its uses in the dye industry. Red rice (known in Chinese as Hung-ch'u or Hongqu) has also been known and used for hundreds of years in China in rice wine making and as a food preservative. In addition, red rice has been known as an ancient Chinese medicine or an ingredient in certain ancient Chinese prescriptions.
Red rice was first used around the time of the Han Dynasty. Tao Gu, who lived in the age of Wudai after the Tang Dynasty, recorded “Red Yeast Rice Cooked with Meat,” in Qing Yi Lu. The method of making red rice was originally recorded in T'ien Kyng K'ai Wu and Pen Ts'ao Kang Mu. A detailed description of the medical applications of red rice was provided in the ancient Chinese pharmacopoeia, Pen Ts'ao Kang Mu, which was published during the Ming Dynasty (1368-1644). In Pen Ts'ao Kang Mu, red rice is described as mild, nonpoisonous, and useful for treating indigestion and diarrhea. Red rice is also described as useful for improving blood circulation and promoting the health of the spleen and stomach. Furthermore, several “prescriptions” using red rice for treating ailments, such as indigestion, diarrhea, and heart and abdominal pains, are also provided in this ancient work. In accordance with the Traditional Chinese Medicine Standard set forth in Pharmacopoeia of People's Republic of China and the Traditional Chinese Medicine standard of Beijing, Nei Monggol, Shandong Province, Jiangsu Province and Hunan Province, etc., red rice is specified to be used as a traditional Chinese medicine. Furthermore, in the textbooks of Chinese universities and colleges such as Food Additives and Food Chemistry, red rice is considered an additive for food and beverages, and has been widely used in the food processing industry for the production of such items as fermented bean curd, beer, and meat.
In an abbreviated English, translation of Pen Ts'ao Kang Mu published in 1911, red rice is described as useful for fermentation and having medicinal value in the treatment of postpartum difficulties in women and dyspeptic conditions in children (Stuart, M. D., in Chinese Materia Medica—Vegetable Kingdom, pages 233-234, republished in 1979 by Southern Materials Center, Inc., Taipei, Republic of China). Red rice, as described in Pen Ts'ao Kang Mu, was subsequently recognized to be the fungal species known as Monascus purpureus Went (Read, B. E., 1936, Chinese Medicinal Plants from the Pen Ts'ao Kang Mu, 3rd edition, published by Peking National History Bulletin; Klein, G., 1932, Handbuch der Pflanzenanalyse II, p. 1422-1423, Wien, Verlag von Julius Springer).
The manufacture of red rice is taught in another publication from the Ming Dynasty, Tien Kung K'ai Wu by Sung Ying-Hsing, which was published in 1637 A. D. (see pages 291-294 in the English translation of this ancient writing, T'ien Kung K'ai Wu—Chinese Technology in the Seventeenth Century, translated by E-tu Zen Sun and Shiou-Chuan Sun, the Pennsylvania State University Press 1966). Red rice is described therein as useful for preserving the color and taste of fish or meat. The manufacturing process used red wine mash and cooked nonglutinous rice as starting materials. The method of making red rice by allowing the fungus to grow on the surface of cooked rice was also recorded by Voderman (1894, Analecta ob Cromatologisch Gebied. II. Geneesh. Fylschrift voor Ned. Indie, 35, No. 5).
Red rice, the fermentation product of Monascus species, is still used in traditional Chinese medicine, wine making and food coloring in Asia and Asian communities in North America. The red and yellow pigments of Monascus purpureus, such as monascorubin and monascin, have been purified and extensively studied (Fielding et al., 1961, J Chem Soc, 4579-4589). The culture conditions and effect on pigmentation of Monascus purpureus have also been studied (Broder et al., 1980, J Food Sci, 45:567-469). Antibacterial activity, especially against Bacillus species, was also detected in Monascus purpureus extract (Wong, 1977, Plant Physiol, 60:578-581). The red rice of the traditional methods has been shown to be of little value and thus has gradually fallen out of use in medical applications.
Osteoporosis is a systemic skeletal disease characterized by low bone mass and deterioration of bone tissue. The effect is the increase in bone fragility and susceptibility to fracture. There are two categories of osteoporosis: primary osteoporosis and secondary osteoporosis. Type I primary osteoporosis, post-menopausal osteoporosis, is characterized by disproportionate loss of trabecular bone. Type II primary osteoporosis is age-associated and affects all skeletal sites, with both cortical and cancellous bone. Type III primary osteoporosis is idiopathic osteoporosis, which affects pre-menopausal women as well as middle-aged and young men.
Secondary osteoporosis is caused by an identifiable agent such as glucocorticoids or by a disease such as hyperthyroidism or myeloma. The most common cause of osteoporosis is estrogen deficiency in post-menopausal women. The major health consequence of osteoporosis is osteoporotic fracture, which may occur at any skeletal site, but the primary sites are the spine, hip and distal forearm. With respect to the definition of persons in need of treatment, a normal person is defined as having a bone mass density (BMD) within one standard deviation (SD) of the young adult mean. A person with the condition of osteopenia is a person having a BMD value of more than one SD, but less than 2.5 SD below the young adult mean. A person with osteoporosis is typically defined as having a BMD value of 2.5 SD or more below the young adult mean.
Historically, the most effective approach to treatment of osteoporosis is through prevention, which is done by optimizing peak bone mass at skeletal maturity, by preventing bone loss or by restoring the bone mineral and architecture in osteoporotic bones. Although peak bone mass is primarily controlled by genetic factors, while growing, the amount of bone tissue that is deposited within the skeleton may be modified by diet, lifestyle or the presence of chronic disease. Bone mass at skeletal maturity can be optimized by intake of calcium, protein, carbohydrates, fat and other nutrients. Exercise and abstinence from tobacco, alcohol and drugs are also beneficial for the skeleton.
Calcium has been shown to be a significant factor for creating optimum bone mass. Increase in calcium intake for post-menopausal women, not yet showing any signs of osteopenia or osteoporosis, is an accepted preventative protocol. Adequate vitamin D is also believed to be helpful since the metabolites of vitamin D are important in the regulation of calcium metabolism. Although vitamin D is found in abundant amounts in fish liver oils and in smaller amounts in oily saltwater fish, egg, butter, margarine and milk, often a daily vitamin D supplement is also necessary to reach the intake level that will prevent vitamin D deficiency.
Once there is onset of osteoporosis, restoration of the skeleton is difficult. Therapeutic options include administration of estrogens in post-menopausal women and administration of bisphosphonates. Varied results have been shown using treatment with vitamin D or its analogs and administration of fluoride.
Accordingly, the choice of protocols for prevention and treatment of osteopenia and osteoporosis is limited. It is therefore desirable to develop more options and more advantageous methods for treating these conditions.